This laboratory has been studying the role of endogenous C-type viruses in natural life processes. Mouse xenotropic C-type viruses have been recovered from adult tissues from animals during malignancy and during normal life. They have also been recovered from mouse embryos as early as the morulae and blastula stage. Both mouse and avian C-type viruses can undergo phenotypic mixing when one cell is infected by both types of viruses. These phenotypically mixed viruses can transfer oncogenic genomes into cells that were previously resistant to them. Genetic studies of mouse strains with a very low level and a very high level of spontaneous xenotropic virus indicate that one to two genes are responsible for this expression of infectious xenotropic virus. The factor which specifically neutralizes xenotropic virus and not ecotropic viruses has been characterized as a high density lipoprotein. It has been purified and antibodies to it have been produced in rabbits. These studies suggest to us that xenotropic virus expression on cells leads to an interaction with neutralizing factor and this interaction effects the normal function of the cell. Similar to the role of protein hormones at the cell surface we believe this virus-factor interaction effects the function of the cell and may be important in normal embryogenesis and development as well as extremes of these processes: autoimmune disease and cancer. BIBLIOGRAPHIC REFERENCES: Levy, J.A., Ihle, J.N., Oleszko, O. and Barnes, R.D. Virus-specific neutralization by a soluble non-immunoglobulin factor found naturally in normal mouse sera. Proc. Nat. Acad. Sci. USA 72: 5071-5075, 1975. Levy, J.A. Endogenous C-type viruses: Double agents in natural life processes. Biomedicine 24: 84-93, 1976.